IDDM is the end result of autoimmune destruction of pancreatic B-cells in a process which progresses over many years. GAD65 has been identified as a major pancreatic B-cell target of autoantibodies. Such antibodies to GAD65 have been detected several years before clinical onset of IDDM, and therefore identify individuals at high risk of developing disease. We hypothesize that IDDM can be prevented by GAD65 specific immuno- intervention in susceptible individuals. The development of immunological tolerance requires analysis.